2-alkoxy-4,5-azimidobenzamides

ABSTRACT

The azimidobenzamides of this invention are useful in the control of emesis. Such azimidobenzamides administered to mammals in a dosage of 250 Mu mg. (as the base) per kilogram of body weight effectuate 100 percent protection against emesis.

United States Patent n 1 Thominet 1 Oct. 1,1974

[ 2-ALKOXY-4,5-AZIMIDOBENZAMIDES [75] Inventor: Michael Leon Thominet,Paris,

France [63] Continuation-impart of Ser. No. 751,737, Aug. 12,

[30] Foreign Application Priority Data Aug. 17, 1967 France 67.118l6lNov. 6, 1967 France 67.127131 52] us. Cl ..260/247.2 A, 260/268 BC,260/293.59, 260/306.7, 260/308 B.

[51] int. Cl C07d 87/42 [58] Field of Search 260/308 B, 29359, 306.7,260/268 BC, 247.2 A

Primary ExaminerDonald G. Dans Assistant ExaminerJose Tovar Attorney,Agent, or FirmFrank M/Nolan [5 7] ABSTRACT The azimidobenzamides of thisinvention are useful in the control of emesis. Such azimidobenzamidesadministeredto mammals in a dosage of 250 p, mg. (as the base) perkilogram of body weight effectuate 100 percent protection againstemesis.

13 Claims, No Drawings 1 2-ALKOXY-4.5-AZIMIDOBENZAMIDES This is acontinuation-in-part application of pending U.S. patent application,Ser. No. 751,737 filed Aug. 12, 1968.

NNH

in which n is 1 or 2 B is alkyl or alkenyl of one to five carbon atoms;and A is a monovalent radical having either of the formulas:

in which m isa whole number less than 4, R is an alkyl group of one tofive carbon atoms, R. and R are hydrogen or 1 or 2 alkyl radicals of oneto five carbon atoms or each is linked together through at least threecarbon atoms to form with the nitrogen to which they are attached aheterocyclic radical with or without oxygen, sulfur or an additionalnitrogen atom. The nitrogen atom has attached thereto hydrogen or analkyl radical of one to five carbon atoms.

Examples of monovalent radicals when formula (2) comprises aheterocyclic radical are pyrrolidinyl, piperidinyl, imidazolidinyl,piperazino and thiazolidinyl.

' Examples of monovalent radicals of formula (3) are pyrrolidinyl andpiperidinyl.

The pharmaceutically acceptable salts of the bases described herein maybe acid addition salts or quaternary ammonium salts. Examples of acidaddition salts are those of the bases and mineral acids, such ashydrochloric acid, hydrobromic acid or phosphoric acid or those of basesand organic acids, such as citric acid, tartaric acid, lactic acid oracetic acid. Examples of quaternary ammonium salts are those obtained byreacting the bases described herein with aliphatic or aromaticalkylating agents such as methyl chloride, methyl bromide, dimethylsulfate, or methyl p-toluenesulfonate.

The compositions of this invention are useful as antiemetics,antispasmodics and analgesics.

It is understood that where the compounds of the invention have one ormore asymmetric carbon atoms, the compound may be the dextro stereoisomer alone, the levo stereo isomer alone or mixtures of both stereoisomers, such as a racemic mixture of both stereo isomers. If aninactive meso form exists, this invention contemplates such meso formwith or without either or both the dextro or levo stereo isomers.

The compounds of this invention are produced by reacting in an acidmedium, such as a mineral acid, a nitrite with a2-alkoxy-4,5-diaminobenzamide having the formula:

in which n, B and A have the same meaning as heretofore defined. Thenitrite may be an organic or inorganic nitrite. Amyl nitrite is anexample of an organic nitrite, while a metallic nitrite, such as analkali metal nitrite (e.g. sodium or potassium nitrite) is an example ofan inorganic nitrite.

Amore comprehensive understanding of this invention is obtained byreference to the following examples.

EXAMPLE I N-(DIETHYLAMINOETHYL )-2-METH OXY-4,5-

' AZIMIDOBENZAMIDE Methyl Stage A nitrobenzoate In a 2 liter flaskequipped with an agitator, a thermometer and a dropping funnel, thereare introduced 223 g. (1 mol) of methyl 2-methoxy-4- acetaminobenzoate,350 ml. of acetic acid and 337 g. of acetic anhydride. The mixture isheated to 40 C. to obtain a clear solution. It is cooled to l520 C. and105 g. (1 mol 50 percent excess) of nitric acid (d=1.49) are poured dropby drop from the dropping funnel. When the introduction is completed themixture is again agitated for 1/2 hour at 40 C., cooled and the reactionmixture poured into 5 liters of water.

There are obtained 182 g. (yield 68 percent) of methyl2-methoxy-4-acetamino-5-nitrobenzoate (m.p. l63-l65 C.).

Stage B N-(diethylaminoethyl)-2-methoxy-4-amino- 5-nitrobenzamidev Intoa 2 liter flask equipped with an agitator and a thermometer there areintroduced 182 g. (0.68 mol) of methyl2-methoxy-4-acetamino-S-nitrobenzoate and 600 ml. of glycol, and then236 g. (0.68 mol X 3) of diethylaminoethylamine are added. The reactionis slightly exothermic (T 31 C.). A suspension is obtained which isheated at 55 C. and at the end of 3/4 of an hour, dissolution iscomplete and U2 hour later the formation of an abundant preprecipitateis observed.

The reaction mixture is maintained for hours at 55 C. All is thensoluble in dilute acetic acid.

Then 600 ml. of water at 40-45 C. are added, under agitation. Then themixture is cooled, the product obtained is dried, washed with 1.3 litersof water and dried at 60 C. 152 G. (yield 63.5 percent) of N-(diethylaminoethyl)-2-methoxy-4-amino-5- nitrobenzamide (m.p. 206208 C.)are obtained. Stage C N-(diethylaminoethyl)-2-methoxy-4,5-diaminobenzamide Into a 2 liter flask equipped with an agitator, athermometer and a dropping funnel, there are introduced 152 g. (0.49mol) of N-(diethylaminoethyl)-2- methoxy-4-amino-S-nitrobenzamide, 230ml. of water and 49 ml. of concentrated hydrochloric acid. A thick massis obtained to which are added 94 g. of tin. The

2-methoxy-4-acetamino-5- mixture is then heated to 50 C. and 390 ml. ofhydrochloric acid are introduced in portions. The reaction is stronglyexothermic. The temperature reaches 80 to 100 C. It is cooled ifnecessary.

When the introduction is complete, it is heated on a water bath untilall the tin is dissolved.

into a 3 liter flask equipped with an agitator, a thermometer and adropping funnel, there are introduced 915 ml. of washing soda. Thenlittle by little the preceding solution is added at about 40 C. The baseseparates in the form of a brown oil. After cooling, it is decanted andthe aqueous solution is extracted with methylene chloride. The organicsolution obtained is washed once with water and dried with potassiumcarbonate. The methylene chloride is then distilled under vacuum to aconstant weight. 137 G. (yield about 100 percent) ofN-(diethylaminoethyl)-2-methoxy-4,5- diaminobenzamide are obtained.

Stage D N-(diethylaminoethyl)-2-methoxy-4,5-

, azimidobenzamide Into a 2 liter flask equipped with an agitator, athermometer and a dropping funnel, there are placed 116 g. (0.284 mol)of dihydrochloride of N- (diethylaminoethyl)-2-methoxy-4,5-diaminobenzamide, 568 ml. of water and 28 ml. of concentratedhydrochloric acid. The mixture is heated at about 40-45 C. to dissolvethe mixture. It is cooled to C. and 20 g. (0.284 mol) of sodium nitratein water are poured drop by drop from the dropping funnel. When theaddition is completed, agitation is continued for 1 hour and thetemperature allowed to rise to 20 C. The solution obtained is treatedwith charcoal, filtered and evaporated to dryness. The solid residue isrecovered in 400 ml. of boiling ethanol. The remaining sodium chlorideis filtered by heat. With cooling and concentration of the alcoholsolution, the hydrochloride of N-(diethylaminoethyl)-2-methoxy-4,5-azimidobenzamide crystallizes. It is dried and washed in alcohol. it isa white solid (m.p. 189191 C) (yield 77.5%).

EXAMPLE II N-(1-ETH YL-2-PYRROLIDYLMETHYL)-2-METHOXY-4,S-AZIMIDOBENZAMIDE Stage A is the same as that described inExample I.

Stage B N-(l-ethyl-2-pyrrolidylmethyl)-2-methoxy- 4-amino-5-nitrobenzamide Into a 2 liter flask equipped with an agitator and athermometer, there are introduced 140 g. (0.52 mol) of methyl2-methoxy-4-acetamino-S-nitro benzoate, 500 ml. of glycol and 201 g.(0.52 mol X 3) of l-ethyl- 2-aminomethylpyrrolidine. A thick yellowsuspension is obtained which is heated to 55C. and maintained at 55 C.for 120 hours. No apparent transformation of the initial precipitate isobserved but at the end of the reaction a sample showed completesolubility in dilute acetic acid.

It is then cooled to about 40 C. and 500 ml. of water are added underagitation. The cooling is completed at about 20 C., the product obtainedis dried, washed with a liter of water and dried at 50 C. 134 G. (yield80 percent) of N-(1-ethyl-2-pyrrolidylmethyl)-2-methoxy-4-amino-S-nitrobenzamide are obtained. (m.p. 188-l90 C.)'

Stage C N-(l-ethyl-2-pyrrolidylmethyl)-2-methoxy- 4,5-diaminobenzamideInto a 2 literflask equipped with an agitator, a thermometer and adropping funnel, there are introduced g. (0.372 mol) ofN-(l-ethyl-2-pyrrolidylmethyl)- 2-methoxy-4-amino-S-nitrobenzamide, 170ml. of waterand 37 ml. of concentrated hydrochloric acid, the mixturebeing heated at 50 C. The hydrochloride formed is completely soluble. 71G. of tin are added and then 290 ml. of concentrated hydrochloric acidare added. The reaction is slightly exothermic. The temperature reaches65 C. At the end of the addition, a thick precipitate forms. It is thenheated on a water bath until all the tin is dissolved.

Into a 2 liter flask equipped with an agitator and a thermometer, thereare introduced 680 ml. of washing soda and then, little by little, theabove mixture without exceeding 40 C. The base separates in the form ofa brown oil and some tin salts are precipitated. 200 Ml. of methylenechloride are added to dissolve the base and filter the mineral salts.

The organic solution is decanted and the aqueous solution is extractedonce with 200 ml. of methylene chloride and once with 100 ml.

The organic solution is washed once with 100 ml. of water and driedwithpotassium carbonate. The methylene chloride is thn distilled undervacuum to a-constant weight. 100 G. (yield 93 percent) of N-(1-ethyl-2-pyrrolidylmethyl)-2-methoxy-4,5-diamino benzamide are obtained.

Stage D N-(1-ethyl-2-pyrrolidylmethyl)-2-methoxy- 4,5-azimidobenzamideIn a 2 liter flask equipped with an agitator, a thermometer and adropping funnel, there are introduced 112 g. (0.278 mol) ofhydrochloride of N-(l-ethyl-Z- pyrrolidylmethyl)-2-methoxy-4,5-diaminobenzamide, 580 ml. of water and 28 ml. of concentrated hydrochlo ricacid. The mixture is heated to 40-45 C. to achieve complete dissolutionand then cooled to 0 C. 19 G. of sodium nitrite dissolved in 28 ml. ofwater are added drop by drop through the dropping funnel. Agitationcontinues for 1 hour at 0 C. and then the temperature is allowed torise. to 20 C. It is evaporated to dryness and the solid residuerecovered in 400 m1. of absolute alcohol, and the sodium chloride formedis filtered with heat. The alcohol solution is concentrated. Thehydrochloride of N-( l-ethyl-2-pyrrolidylmethyl)-2-methoxy-4,5-azimidobenzamide' formed crystallizes. It is dried, washed withalcohol and then with ether. 55 G. (yield: 85 percent) of product in theform of white crystals are obtained. (m.p. 197-200 C.)

To produce N-(1-ethyl-2-pyrrolidylmethyl)-2- vinyloxy-4,5azimidobenzamide, Example I1 is followed except that the addition of 146g. (0.52 mol) of 2- vinyloxy-4-acetamino-S-nitromethyl benzoate isemployed instead of the g. of 2-methoxy-4-acetamino- 5-nitromethylbenzoate.

To produce N-(1-ethyl-2-imidazolidylmethyl)-2-methoxy-4,5-azimidobenzamide, Example II is followed except that theaddition of 202 g. (0.52 mol X 3) of l-ethyl-2-aminomethylimidazolidineis employed instead of the 201 g. of 1-ethyl-2-aminomethylpyrrolidine.

To produce N-(3-ethyl-2-thiazolidylmethyl)-2-methoxy-4,5-azimidobenzamide, Example II is followed except that theaddition of 229 g. (0.52 mol X 3) of 3-ethyl-2-aminomethylthiazolidineis employed instead of the 201 g. of 1-ethyl-2-aminomethyl pyrrolidine.

EXAMPLE III DEXTRO N-(1-ETHYL-Z-PYRROLIDYLMETHYL)-2-METHOXY-4,5-AZIMIDOBENZAMIDE Stage A is similar to that described inExample I. Stage B Dextro N-(1-ethyl-2-pyrrolidylmethyl)-2-methoxy-4-amino-5-nitrobenzamide In a 2 liter flask equipped withanagitator and a thermometer, there are introduced 80 g. (0.3 mol) ofmethyl 2-methoxy-4-acetamino-5-nitrobenzoate, 285 ml. of glycol and 84g. (2.2 X 0.3 mol) of dextro 1- ethyl-2-amino-methylpyrrolidine.

A yellow suspension is obtained which is heated at 55 C. and maintainedat that temperature for 216 hours.

Then it is cooled to 40 C. and 500 ml. of water are added withagitation. Cooling is completed at about 20 C., the product obtained isdried, washed with 1 liter of water and dried at 50 C. 45 G. of dextroN-( 1-ethyl-2- pyrrolidylmethyl)-2-methoxy-4-amino-5- nitrobenzamide(mp. 185-187C.) are obtained. Stage C DextroN-(1-ethyl-2-pyrrolidylmethyl)-2- methoxy-4,S-diaminobenzamide Thereduction of 150 g. (0.4 mol) of hydrochloride of dextro N-(l-ethyl-2-pyrrolidylmethyl)-2-methoxy-4- amino-S-nitrobenzamide iseffectuated in an autoclave with alcohol at 95 C. and in the presence ofRaney nickel as a catalyst. The reaction lasts 1 hour. The hydrogenpressure at the beginning is 64 kg. at 45 C.

At the end of the reaction, the temperature reached 83 C. The nickel isfiltered with heat and the dihydrochloride is prepared with the aid of40 ml. of concentrated hydrochloric acid. After recrystallization inalcohol, 100 g. of hydrochloride of dextro N-(l-ethyl-2-pyrrolidylmethyl)-2-methoxy-4,5-diaminobenzamide are obtained. (Yield:70 percent) (mp. 215 C.) Stage D DextroN-(1-ethyl-2-pyrrolidylmethyl)-2- methoxy-4,5-azimidobenzamide In a 1liter flask equipped with an agitator, a thermometer, and a droppingfunnel, there are introduced 43 g. (0.107 mol) of hydrochloride ofdextro N-(lethyl-Z-pyrrolidylmethyl)-2-methoxy-4,5-- azimidobenzamide,215 ml. of water and 11 ml. of concentrated hydrochloric acid. Themixture is heated to 55 C. to achieve complete dissolution. Then it iscooled to 0C. 7.5 G. (0.107 mol) of sodium nitrite dissolved in ml. ofwater are added drop by drop from the dropping funnel. Agitation iscontinued for 1 hour at 0 C. and then the mixture is allowed to returnto room temperature.

The alcohol solution is concentrated. The hydrochloride of benzamideformed crystallizes, is dried, washed with alcohol and then with ether.There are obtained 23 g. (yield 63 percent) of hydrochloride of dextroN- 6 1-ethyl-2-pyrrolidylmethyl )-2-methoxy-4,5- azimidobenzamide (m.p.l-172 C. )-[a],, =+5 (5 percent aqueous solution).

EXAMPLE IV LEVO N-(1-ETI-IYL-2-PYRROLIDYLMETHYL)-2-METHOXY-4,S-AZIMIDOBENZAMIDE Following the procedure in Example III, butreplacing the dextro-amine with the levo-amine,there is obtained thedihydrochloride of levo N-( l-ethyl-2-pyrrolidylmethyl)-2-methoxy-4,5-azimidobenzamide, with the followingcharacteristics:

(m.p. 170172 C.)

[04],, 5 4 (5 percent aqueous solution) EXAMPLE VN-(ETHYL-PROPYLAMINOETI-IYL)-2- METHOXY-4,5-AZIMIDOBENZAMIDE Stage A isthe same as in Example I.

Stage B N-(ethyl-propylaminoethyl)-2-methoxy-4- amino-5-nitrobenzamideIn a 2 liter flask equipped with an agitator and a thermometer, thereare introduced 188 g. (0.7 mol) of methyl2-methoxy-4-acetamino-5-nitrobenzoate and 700 ml. of glycol, and then273 g. (0.7 mol X 3) of ethyl-propylethylene diamine are added.

The suspension obtained is heated at 55 C. and that temperature ismaintained for 72 hours.

The ester dissolves partially at the beginning of the reaction andthebenzamide formed begins to precipitate. At the end of the reaction,there is total solubility.

added. The mixture is heated at 55 C. and 390 ml. of I concentratedhydrochloric acid are added in small portions. The reaction is stronglyexothermic. When the introduction is terminated, the mixtureis heated ona water bath until the tin is totally dissolved.

Into a 3 liter flask equipped with an agitator, a thermometer and adropping funnel, there are introduced 915 ml. of washing soda and then,little by little, the preceding solution without exceeding 40 C. Thebase separates in the form of a paste which is redissolved in 150 ml. ofmethylene chloride. The aqueous solution is extracted with methylenechloride. The organic solution obtained is washed with water and driedwith potassium carbonate. The methylene chloride is then distilled undervacuum to a constant weight. 131 G. (yield percent)of-N-(ethyl-propylaminoethyl)-2-methoxy- 4,5-diaminobenzamide areobtained.

Stage D N-(ethyhpropylaminoethyl)-2-methoxy- 4,5-azimidobenzamide Into a2 liter flask equipped with an agitator, a thermometer and a droppingfunnel, there are introduced 106 g. (0.258 mol) of dihydrochloride-ofN-(ethylpropylaminoethyl )-2-methoxy-4,5-diaminobenzamide, 516 ml. ofwater and 26 ml. of concentrated hydrochloric acid. It is heated todissolve the mixture. It is then cooled at C. and 18 g. (0.258 mol) ofsodium nitrite dissolved in 20 ml. of water is poured drop by drop fromthe dropping funnel. When the addition is completed, the mixture ismaintained under agitation at 0 C. for 1 hour, and then allowed toreturn to room temperature.

The solution is then treated with charcoal, filtered 8 taken'up with 200ml. of boiling absolute alcohol. The sodium chloride is filtered off andalcohol is distilled. The hydrochloride crystallizes. It is drained,washed with alcohol, and dried, to yield 35 g. of N-(piperidinoethyl)-2-methoxy-4,5-azimidobenzamide LD in mg/kg ofcomposition in base state COMPOSITIONS by intraintraperisubcutamouthvenously toneally neously N-(diethylaminoethyl) I500 l43-l46 387-400600-576 -2-methoxy-4,5- (30% azimidobenzamide mortality) N-( l-ethyl-2-pyrl5 17 69 2 l 4-2l6 330-32] rolidylmethyl)-2-methoxy-4,5-azimidobenzamide Dextro-N-( l-ethyl-2- 84-85 248 339pyrrolidylmethyl)-2- methoxy-4,5-azimidobenzamide Levo-N-(l-ethyl-2-83-84 207 243 pyrrolidylmethyh- 2-methoxy-4,5- azimidobenzamide andevaporated to dryness. The solid residue is recov ered with 300 ml. ofboiling ethanol. The remaining sodium chloride is filtered with heat.After cooling and concentration of the alcohol solution, thehydrochloride of N-(ethyl-propylaminoethyl)-2-methoxy-4,5-azimidobenzamide crystallizes. It is dried and washed with alcohol. Itis a white solid (mp. 155 C.).

EXAMPLE VI IODOMETHYLATE OF N-( DIETHYLAMINOETHYL )-2-METHOXY-4,5-AZIMIDOBENZAMIDE Into a 250 ml. flask, there are introduced 33 g. (0.113mol) of N-(diethylaminoethyl)-2-methoxy-4,5- azimidobenzamide dissolvedin 66 ml. of methyl alcohol and 19 g. (0.113 mol 20 percent) of methyliodide dissolved in 38 ml. of methyl alcohol. These are mixed and theflask is left securely closed for 136 hours. The product crystallizes.It is dried and then recrystallized in acetone and there is finallyobtained iodomethylate of N-(diethylaminoethyl)-2-methoxy-4,5-azimidobenzamide (mp. 205 C.).

EXAMPLE VII N-( PlPERIDlNOETl-IYL)-2-METHOXY-4,5- AZIMIDOBENZAMIDEHYDROCHLORIDE In a 1 liter flask are mixed N-piperidinoethyl-2-methoxy-4,5-diaminobenzamide dihydrochloride (53 g.), 288 ml. of waterand 14 ml. of hydrochloric acid (d= 1.18). The mixture is warmed at 45C. to dissolve and then cooled to 0 C. Sodium nitrite g.) dissolved inml. of water is introduced while the temperature is maintained at 0 C.Stirring is continued for one hour and the temperature is then allowedto rise to 18 C. Water is distilled under vacuum and the residue Theanti-emetic action of these compositions on the Rate of protection indose of 250 u/kg (base) COMPOSITIONS N-(diethylaminoethyl)-2-methoxy-4,5-azimidohenzamide N-( l-ethyl-2-pyrrolidylmethyl)2-methoxy-4,5 -azimidobenzamide Dextr0-N-(l-ethyl-Z-pyrrolidylmethyl)-2-methoxy-4,5- azimidobenzamide Levo-N-(l-ethyl-2-pyrrolidylmethyl)-2-methoxy-4,5- azimidobenzamide Thecompositions of this invention have the interesting pharmacologicalproperty of being anti-cataleptic. For two compositions of thisinvention, the cataleptic activity of the product showed the followingresults: (results measured at the maximum of the effect, such as after300 to 360 minutes) azimidobenzamide The experimental results wereclinically confirmed, the products being administered in the form oftablets or ampules of a pharmaceutically acceptable salt.

The treatments were given only under clinical conditions correspondingto pharmacodynamics, with no manifestation of medicinal intolerance. Thevomitings stopped quickly and did not recur after cessation oftreatment. For example, to a 70 year old man with serious recto-colitishaving repeated attacks of vomiting at the time of feeding, 2 ampulesdaily of mg. of hydrochloride of N-(diethylaminoethyl)-2-methoxy-4,5-azimidobenzamide were adminstered. The tolerance was excellent and in 2days there was a very great diminution of vomiting, allowing the feedingof the patient. Vomiting stopped completely after 4 days of treatment.

In a 55 year old woman afflicated with mammary cancer and treated withother medication, severe vomiting stopped in two days after theadministration of 3 ampules per day of 10 mg. of the hydrochloride of N-1-ethyl-2-pyrrolidylmethyl)-2-methoxy-4,5- azimidobenzamide.

The antiemetic compositions of this invention can be administered in theform of a pharmaceutically acceptable salt in coated pills, injectableampules or aerosols, suppositories, granulated saccharine or sweetenedsyrup. 7

What is claimed is:

l. A compound of the formula:

' M cosh-Ema N NH in which n is 1 when A is a heterocyclic radical or 2when A is a non-heterocyclic radical; B is methyl; and A is:

3-ethyl-2-thiazolidyl-,

l-ethyfi-imidazolidyb,

4-ethyl-2-morpholinyl-, or l-ethyl-2-piperazinyl-, R is alkyl of one tofive carbon atoms, R and R are ethyl or propyl or pharmaceuticallyacceptable salts thereof.

2. A compound of claim 1 which is a dextro isomer.

9. A compound of claim 1 which is iodomethylate of N-(diethylaminoethyl)-2-methoxy-4,5- azimidobenzamide.

10. A compound of claim 1 which is N-(1-ethyl-2-imidazolidylmethyl)-2-methoxy-4,5- azimidobenzamide.

11. A compound of claim 1 which is N-(3-ethyl-2-thiazolidylmethyl)-2-methoxy-4,5-azimidobenzamide.

12. A compound of claim 1 which is N-(4-ethyl-2-morpholinylmethyl)-2-methoxy-4,5- azimidobenzamide.

13. A compound of claim 1 which is N-(l-ethyl-2-piperazinylmethyl)-2-methoxy-4,5-azimidobenzamide.

1. A COMPOUND OF THE FORMULA:
 2. A compound of claim 1 which is a dextroisomer.
 3. A compound of claim 1 which is a levo isomer.
 4. A compoundof claim 1 which isN-(diethylaminoethyl)-2-methoxy-4,5-azimidobenzamide.
 5. A compound ofclaim 1 which isN-(1-ethyl-2-pyrrolidyl-methyl)-2-methoxy-4,5-azimidobenzamide.
 6. Acompound of claim 1 which is dextroN-(1-ethyl-2-pyrrolidylmethyl)-2-methoxy-4,5-azimidobenzamide.
 7. Acompound of claim 1 which is levoN-(1-ethyl-2-pyrrolidylmethyl)-2-methoxy-4,5-azimidobenzamide.
 8. Acompound of claim 1 which isN-(ethyl-propylaminoethyl)-2-methoxy-4,5-azimidobenzamide.
 9. A compoundof claim 1 which is iodomethylate ofN-(diethylaminoethyl)-2-methoxy-4,5-azimidobenzamide.
 10. A compound ofclaim 1 which isN-(1-ethyl-2-imidazolidylmethyl)-2-methoxy-4,5-azimidobenzamide.
 11. Acompound of claim 1 which isN-(3-ethyl-2-thiazolidylmethyl)-2-methoxy-4,5-azimidobenzamide.
 12. Acompound of claim 1 which isN-(4-ethyl-2-morpholinylmethyl)-2-methoxy-4,5-azimidobenzamide.
 13. Acompound of claim 1 which isN-(1-ethyl-2-piperazinylmethyl)-2-methoxy-4,5-azimidobenzamide.